Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women

This randomized, placebo-controlled clinical trial evaluated the endocrine and metabolic effects of long-term sermorelin (GHRH(1-29)-NH2) administration in 19 healthy subjects aged 55 to 71 years. Treatment consisted of subcutaneous sermorelin injections before bedtime for 5 months, aiming to restore age-related growth hormone (GH) secretion.

Results demonstrated significant effects on the GH/IGF-I axis:

• Significant increase in nocturnal GH secretion
• Elevated IGF-I (insulin-like growth factor type I) levels
• Increased IGFBP-3 (IGF-binding protein type 3)
• Partial restoration of the pulsatile GH pattern characteristic of younger individuals

At the metabolic and clinical level, sermorelin produced:

• Increased lean body mass
• Improved insulin sensitivity
• In men: improved general well-being and libido
• Trend toward reduced body fat

An important aspect of this study is that sermorelin, unlike direct recombinant GH administration, preserves the physiological negative feedback of the somatotropic axis. This means the resulting GH secretion remains under the control of endogenous regulatory mechanisms, reducing the risk of supraphysiological levels. The study was one of the first to demonstrate that stimulating the GH axis via GHRH can partially reverse age-related metabolic changes in a more physiological manner than direct GH replacement.